Major Areas of Research
- Studies of molecular biology, immunobiology, and pathogenesis of the human respiratory pathogens respiratory syncytial virus (RSV), human parainfluenza virus (HPIV) serotypes 1, 2, and 3, and human metapneumovirus (HMPV)
- Studies involve infection in vitro of epithelial cells, macrophages, and other cell types and in vivo infection of experimental animals to elucidate the viral replicative cycle, interactions between viral and host components, the host response to infection, and mechanisms of pathogenesis.
- Development of live-attenuated RSV, HPIV3, and HMPV vaccine candidates
- Vaccine candidates are designed to contain well-defined attenuating mutations and are generated from cDNA by “reverse genetics”. Candidates are evaluated preclinically in monolayer cell cultures, in vitro models of airway epithelium, rodents, and nonhuman primates.
- Evaluation of candidate live vaccines in clinical studies with clinical collaborators, as well as wild type viruses in adult volunteers
- Development of vaccine vectors based on HPIV and avian paramyxoviruses (APMVs) for use against highly pathogenic emerging viruses including SARS Coronavirus 2, avian influenza, and Ebola viruses
We study the molecular virology, pathogenesis, and immune response of human respiratory pathogens, including RSV, HPIV serotypes 1, 2, and 3, and HMPV. These are enveloped, cytoplasmic viruses with single-stranded negative-sense RNA genomes of 13-19 kb. The laboratory investigates basic features of viral molecular biology, pathogenesis, and immunobiology of these viruses that provide an intellectual foundation for translational vaccine studies.
The pneumovirus RSV is a leading worldwide agent of respiratory tract disease, especially in young infants. The laboratory also studies several other major pediatric respiratory pathogens, namely HPIV1, 2, and 3 and HMPV. Other areas of interest include other pathogens of the paramyxoviridae and pneumoviridae families. The laboratory is using reverse genetics to design live, attenuated vaccines for RSV, HPIV3, and HMPV for intranasal administration to infants as pediatric vaccines. In studies supported in part by collaboration with industry, lead candidates for RSV and HPIV3 are in Phase I, and in some cases Phase II, clinical trials. The laboratory also is using paramyxoviruses and pneumoviruses as vaccine vectors to express protective antigens of emerging pathogens. In 2020, we expanded our program to include the development of vector vaccine candidates against SARS-CoV-2.
Dr. Buchholz received her Ph.D. in 1994 from the Free University of Berlin, Germany. She conducted postdoctoral studies at the Federal Research Center of Virus Diseases of Animals in Tuebingen, Germany, and became a tenured scientist at the Federal Research Center in 2000. In 2002, she joined Dr. Peter L. Collins’ section in the Laboratory of Infectious Diseases, and she became the Chief of the RNA Viruses Section in 2020.
- American Society for Virology
- American Society for Microbiology
- International RSV Society
- Pneumoviridae study group, International Committee on Taxonomy of Viruses
Laura Ahlers, Sharmin Afroz, Sonja Barbagallo, Bibha Dahal, Jaclyn Kaiser, Cyril Le Nouen, Xueqiao Liu, Cindy Luongo, Thomas McCarty, Shirin Munir, Hongsu Park, Celia Santos, Lijuan Yang, Jessica Chen, Megan Levy, Jana Liese
Karron RA, Luongo C, Mateo JS, Wanionek K, Collins PL, Buchholz UJ. Safety and Immunogenicity of the Respiratory Syncytial Virus Vaccine RSV/DeltaNS2/Delta1313/I1314L in RSV-Seronegative Children. J Infect Dis. 2020 Jun;222(1):82-91.
McFarland EJ, Karron RA, Muresan P, Cunningham CK, Libous J, Perlowski C, Thumar B, Gnanashanmugam D, Moye J, Schappell E, Barr E, Rexroad V, Fearn L, Spector SA, Aziz M, Cielo M, Beneri C, Wiznia A, Luongo C, Collins P, Buchholz UJ. Live Respiratory Syncytial Virus Attenuated by M2-2 Deletion and Stabilized Temperature Sensitivity Mutation 1030s Is a Promising Vaccine Candidate in Children. J Infect Dis. 2020 Feb;221(4):534-543.
Lingemann M, McCarty T, Liu X, Buchholz UJ, Surman S, Martin SE, Collins PL, Munir S. The alpha-1 subunit of the Na+,K+-ATPase (ATP1A1) is required for macropinocytic entry of respiratory syncytial virus (RSV) in human respiratory epithelial cells. PLoS Pathog. 2019 Aug;15(8):e1007963.
Le Nouën C, McCarty T, Brown M, Smith ML, Lleras R, Dolan MA, Mehedi M, Yang L, Luongo C, Liang B, Munir S, DiNapoli JM, Mueller S, Wimmer E, Collins PL, Buchholz UJ. Genetic stability of genome-scale deoptimized RNA virus vaccine candidates under selective pressure. Proc Natl Acad Sci USA. 2017 Jan;114(3):E386-E95.
Karron RA, Luongo C, Thumar B, Loehr KM, Englund JA, Collins PL, Buchholz UJ. A gene deletion that up-regulates viral gene expression yields an attenuated RSV vaccine with improved antibody responses in children. Sci Transl Med. 2015 Nov;7(312):312ra175.
Le Nouën C, Hillyer P, Winter CC, McCarty T, Rabin RL, Collins PL, Buchholz UJ. Low CCR7-mediated migration of human monocyte derived dendritic cells in response to human respiratory syncytial virus and human metapneumovirus. PLoS Pathog. 2011 Jun;7(6):e1002105.
Le Nouen C, Buchholz UJ, Collins PL, Mueller S, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services and Codagenix, Inc., assignees. Vaccine candidates for human respiratory syncytial virus (RSV) having attenuated phenotypes. United States patent US 10,808,012. 20 Oct 2020.
Collins, PL, Luongo, C, Buchholz UJ, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Recombinant Respiratory Syncytial Virus Strains with Mutations in the M2-2 ORF Providing a Range of Attenuation Phenotypes. United States Patent no. US 10,655,109. 19 May 2020.
Collins, PL, Liang, B, Munir, S, Schaap-Nutt, A, Buchholz UJ, Mackow, N, Kwong, P, Graham B, McLellan, J, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Recombinant Bovine/Human Parainfluenza Virus 3 (B/HPIV3) Expressing a Chimeric RSV/BPIV3 F Protein and Uses Thereof. United States Patent no. US 10,654,898. 19 May 2020.
Collins, PL, Luongo, C, Buchholz UJ, Murphy, BR, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Genetically stable live attenuated respiratory syncytial virus vaccine and its production. United States Patent no. US 10,307,476. 4 June 2019.
Buchholz U, Collins PL, Murphy BR, Whitehead SS, Krempl CD, inventors; The United States of America as represented by the Secretary, Department of Health and Human Services, assignee. Production of attenuated, human-bovine chimeric respiratory syncytial virus vaccines. United States patent US 7,842,798. 30 Nov 2010.
Krempl CD, Collins PL, Murphy BR, Buchholz U, Whitehead SS, inventors; The United States of America as represented by the Department of Health and Human Services, assignee. Respiratory syncytial virus vaccines expressing protective antigens from promotor-proximal genes. United States patent US 7,744,902. 29 Jun 2010.